87443-64-9Relevant academic research and scientific papers
Design, Synthesis, and Biological Evaluation of Tetrahydroisoquinoline-Based Histone Deacetylase 8 Selective Inhibitors
Taha, Taha Y.,Aboukhatwa, Shaimaa M.,Knopp, Rachel C.,Ikegaki, Naohiko,Abdelkarim, Hazem,Neerasa, Jayaprakash,Lu, Yunlong,Neelarapu, Raghupathi,Hanigan, Thomas W.,Thatcher, Gregory R. J.,Petukhov, Pavel A.
supporting information, p. 824 - 829 (2017/08/16)
Histone deacetylase 8 (HDAC8) is a promising drug target for multiple therapeutic applications. Here, we describe the modeling, design, synthesis, and biological evaluation of a novel series of C1-substituted tetrahydroisoquinoline (TIQ)-based HDAC8 inhibitors. Minimization of entropic loss upon ligand binding and use of the unique HDAC8 "open" conformation of the binding site yielded a successful strategy for improvement of both HDAC8 potency and selectivity. The TIQ-based 3g and 3n exhibited the highest 82 and 55 nM HDAC8 potency and 330- and 135-fold selectivity over HDAC1, respectively. Selectivity over other class I isoforms was comparable or better, whereas inhibition of HDAC6, a class II HDAC isoform, was below 50% at 10 μM. The cytotoxicity of 3g and 3n was evaluated in neuroblastoma cell lines, and 3n displayed concentration-dependent cytotoxicity similar to or better than that of PCI-34051. The selectivity of 3g and 3n was confirmed in SH-SY5Y cells as both did not increase the acetylation of histone H3 and α-tubulin. Discovery of the novel TIQ chemotype paves the way for the development of HDAC8 selective inhibitors for therapeutic applications.
CATALYST COMPOUNDS
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Paragraph 0293; 0295, (2015/03/16)
The present invention relates to an iridium-based catalyst compound for hydrogenating reducible moieties, especially imines and iminiums, the catalyst compounds being defined by the formula: (Formula (I)) where ring B is a conjugated ring system with one or more substituents. The catalysts of the invention are particularly effective in reductive amination procedures which involve the in situ generation of the imine or iminium under reductive hydrogenative conditions.
A highly active cyclometallated iridium catalyst for the hydrogenation of imines
Villa-Marcos, Barbara,Tang, Weijun,Wu, Xiaofeng,Xiao, Jianliang
supporting information, p. 6934 - 6939 (2013/10/08)
A cyclometallated iridium complex containing an imino ligand has been shown to catalyse the hydrogenation of imines. The catalyst is highly active and selective for imino bonds, with a wide variety of imines being hydrogenated in less than 1 hour at a substrate/catalyst (S/C) ratio of 2000 at 20 bar H 2 pressure and 75 °C.
Robust cyclometallated Ir(iii) catalysts for the homogeneous hydrogenation of N-heterocycles under mild conditions
Wu, Jianjun,Barnard, Jonathan H.,Zhang, Yi,Talwar, Dinesh,Robertson, Craig M.,Xiao, Jianliang
supporting information, p. 7052 - 7054 (2013/09/02)
Cyclometallated Cp*Ir(N∧C)Cl complexes derived from N-aryl ketimines are highly active catalysts for the reduction of N-heterocycles under ambient conditions and 1 atm H2 pressure. The reaction tolerates a broad range of other potentially reducible functionalities and does not require the use of specialised equipment, additives or purified solvent.
CATALYST COMPOUNDS
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Paragraph 00137; 00139, (2013/11/05)
The present invention relates to an iridium-based catalyst compound for hydrogenating reducible moieties, especially imines and iminiums, the catalyst compounds being defined by the formula: (Formula (I)) where ring B is a conjugated ring system with one or more substituents. The catalysts of the invention are particularly effective in reductive amination procedures which involve the in situ generation of the imine or iminium under reductive hydrogenative conditions.
Facile synthesis and in vitro properties of 1-alkyl- and 1-alkyl-N-propargyl-1,2,3,4-tetrahydroisoquinoline derivatives on PC12 cells
Kitabatake, Michikazu,Nagai, Junko,Abe, Kenji,Tsuchiya, Yukihiro,Ogawa, Keita,Yokoyama, Takashi,Mohri, Kunihiko,Taguchi, Kyoji,Horiguchi, Yoshie
experimental part, p. 4034 - 4043 (2009/12/04)
The synthesis of several 1-alkyl-1,2,3,4-tetrahydroisoquinolines, which may play an important role in Parkinson's disease, has been achieved by modified Pictet-Spengler cyclization of the formyliminium ion. The direct cytotoxicity and preventative effects
Synthesis and in vitro cytotoxicity of 1,2,3,4-tetrahydroisoquinoline derivatives
Saitoh, Toshiaki,Abe, Kenji,Ishikawa, Masami,Nakatani, Masanao,Shimazu, Seiichiro,Satoh, Noriyuki,Yoneda, Fumio,Taguchi, Kyoji,Horiguchi, Yoshie
, p. 241 - 252 (2007/10/03)
Several 1-alkyl-1,2,3,4-tetrahydroisoquinoline (TIQ) derivatives, which may play a role in Parkinson's disease, have been synthesized via Pummerer-type cyclization of the sulfonium ion formed in situ from N-formyl sulfoxide. Using an in vitro trypan blue
Synthesis and antimuscarinic properties of quinuclidin-3-yl 1,2,3,4-tetrahydroisoquinoline-2-carboxylate derivatives as novel muscarinic receptor antagonists
Naito, Ryo,Yonetoku, Yasuhiro,Okamoto, Yoshinori,Toyoshima, Akira,Ikeda, Ken,Takeuchi, Makoto
, p. 6597 - 6606 (2007/10/03)
In the course of continuing efforts to develop potent and bladder-selective muscarinic M3 receptor antagonists, quinuclidin-3-yl 1-aryl-1,2,3,4-tetrahydroisoquinoline-2-carboxylate derivatives and related compounds were designed as conformationally restricted analogues of quinuclidin-3-yl benzhydrylcarbamate (8). Binding assays with rat muscarinic receptor subtypes revealed that the quinuclidin-3-yl 1-aryl-1,2,3,4- tetrahydroisoquinoline-2-carboxylate derivatives showed high affinities for the M3 receptor, and selectivity for the M3 receptor over the M2 receptor. Of these derivatives, (+)-(1S,3'R)-quinuclidin-3'-yl 1-phenyl-l,2,3,4-tetrahydroisoquinoline-2-carboxylate monohydrochloride (9b) exhibited almost the same inhibitory activity against bladder contraction to that of oxybutynin (1), and more than 10-fold selectivity for bladder contraction versus salivary secretion, demonstrating that 9b may be useful for the treatment of symptoms associated with overactive bladder without having side effects such as dry mouth.
Phencyclidine-like Effects of Tetrahydroisoquinolines and Related Compounds
Gray, Nancy M.,Cheng, Brian K.,Mick, Stephen J.,Lair, Cecelia M.,Contreras, Patricia C.
, p. 1242 - 1248 (2007/10/02)
A series of 1,2,3,4-tetrahydroisoquinolines, tetrahydrothienopyridines, and related compounds were evaluated for their ability to inhibit binding of -1--N-allylnormetazocine to phencyclidine (PCP) and ? receptors, respectively.A representative series of compounds was evaluated in behavioral assays to determine the ability of the compounds to induce PCP-like stereotyped behavior and ataxia.All of the compounds caused stereotyped behavior and ataxia, indicating their agonist actions at the PCP site.
ALKYLATION OF THE ISOQUINOLINE SKELETON IN THE 1-POSITION: LITHIATED 2-PIVALOYL- AND 2-BIS(DIMETHYLAMINO)-PHOSPHINOYL-1,2,3,4-TETRAHYDROISOQUINOLINES
Seebach, Dieter,Lohmann, Jean-Jacques,Syfrig, Max A.,Yoshifuji, Masaaki
, p. 1963 - 1974 (2007/10/02)
Nucleophilic reactivity in the 1-position of 1,2,3,4-tetrahydroisoquinoline is generated by lithiation of the N-pivaloyl- (16a) and N-phosphinoyl-derivatives (17a).The organolithium compounds (16b, 17b) thus obtained are highly nucleophilic and can be alkylated even with poor alkylating reagents such as secondary halides, neopentyl bromide and cyclopentanone.Hydrolysis of the phosphorylamide products with hydrochloric acid leads to 1-substituted tetrahydroisoquinolines in excellent yields (Table 2).
